Objective To investigate the expression alteration and significance of long non-coding RNA (lncRNA)by GWAS(Genome-wide association study)between Esophageal squamous cell carcinoma(ESCC)and its adjacent normal esophageal tissues. Methods lncRNA and mRNA differential expression in 6 pairs of ESCC and matched non-cancerous tissues were screened by microarray assay. The target genes were predicted. Finally , GO(Gene Ontology)and Pathway analysis was used for the further research of lncRNA. Results A total of 680 lncRNA and 1472mRNA were differentially expressed at more than two-fold change(P ≤ 0.05,with 161lncRNA and 653mRNA up-regulated,519lncRNA and 819mRNA down-regulated between ESCC and its adjacent normal esophageal tissues. Gene ontology and pathway analysis results suggested that the differentially expressed genes were involved in 11 pathways.Theyare potentially associated with esophageal squamous cell carcinoma ,including post-translational protein modification ,mucin type O-Glycan biosynthesis and sphingolipid metabolism pathways , which mainly related to the changes of molecular function ,cellular components and biological processes. Through cis and trans analysis,a total of 15 differentially expressed lncRNA had cis-and/or trans-regulated target genes in the database,with 13 lncRNA had cis-regulated target genes,3 lncRNA had trans-regulated target genes,and 1 lncRNA had both cis- and trans-regulated target genes. Conclusion Compared with adjacent normal tissues ,a large number of lncRNA were expressed differentially in ESCC in Xinjiang Han people.Aberrantly expressed lncRNA may play important roles in ESCC development and progression through some signaling pathways ,which are of great significance for further search of new targets for the diagnosis and treatment of ESCC.

Objective To investigate the risk factors of slow coronary flow (SCF) phenomenon; To study the prognosis of SCF patients and analyze the high risk factors of adverse events by follow-up.Methods 17930 patients were analyzed retrospectively who had undergone routine coronary angiography because of suspected coronary artery disease at TEDA International Cardiovascular Hospital from January 2006 to December 2010.By Thrombolysis in myocardial infarction Frame Count method,236 patients with normal coronary artery but slow coronary flow were enrolled in the SCF group and 240 patients with normal coronary artery and normal coronary flow (40-50patients per year) were enrolled in the control group.After that,the risk factors leading to SCF were analyzed by the multivariate logistic regression analysis and all patients were followed up from March 2012 to April 2012 to know about the incidence of adverse events (acute coronary syndrome,malignant arrhythmia and sudden cardiac death) and the high risk factors leading to the adverse events.Results (1) Compared to the patients in the control group,the patients in SCF group have higher percentage of male (76.69％ vs.42.08％,P =0.000) 、rate of smokers (58.48％ vs.27.50％,P =0.000) 、BMI (26.78 ±3.75 vs.26.13 ±3.20,P =0.043) 、serum uric acid (344.90 ± 86.18 vs.304.43 ±76.44,P =0.000) 、serum creatinine (68.27 ± 15.10 vs.60.92 ± 13.17,P =0.000)、triglyceride (1.85 ± 1.23 vs.1.65 ± 0.81,P =0.037) but younger age and lower high density lipoprotein cholesterol (1.14 ± 0.28 vs.1.19 ± 0.30,P =0.048).(2) By multivariate logistic regression analysis,male,smoking status,hiah BMI and serum uric acid are all independent factors for SCF.(3) The SCF phenomenon noted in lvessel,2 vessels and 3 vessels accounted for 7.29％,26.04％,66.67％,respectively.(4) During the follow-up,2 patients with malignant arrhythmia and 1 patients with ACS were found in SCF group,no sudden cardiac death took place.None of the adverse events happened in the control group.Conclusions Younger male smokers are prone to have SCF,high BMI and serum uric acid are also independent factors for SCF; The SCF phenomenon is most common in three coronary arteries.Both malignant arrhythmia and acute coronary syndrome took place in the SCF group in the follow-up.

Cell therapy has achieved tremendous success in regenerative medicine in the past several decades. However, challenges such as cell loss, death and immune-rejection after transplantation still persist. Biomaterials have been designed as carriers to deliver cells to desirable region for local tissue regeneration; as barriers to protect transplanted cells from host immune attack; or as reactors to stimulate host cell recruitment, homing and differentiation. With the assistance of biomaterials, improvement in treatment efficiency has been demonstrated in numerous animal models of degenerative diseases compared with routine free cell-based therapy. Emerging clinical applications of biomaterial assisted cell therapies further highlight their great promise in regenerative therapy and even cure for complex diseases, which have been failed to realize by conventional therapeutic approaches.
Animals ; Biocompatible Materials ; chemistry ; pharmacology ; Bioreactors ; Cell- and Tissue-Based Therapy ; adverse effects ; methods ; Drug Carriers ; chemistry ; pharmacology ; Humans ; Regenerative Medicine ; methods

Lacunar stroke is one of the most common ischemic stroke types in clinical practice at present. Its prognosis is generally better. However, studies have shown that about 20％ ～30％ of patients with lacunar stroke may have early neurological deterioration. This article reviews the pathophysiological mechanisms and predictors of early neurological deterioration in patients with lacunar stroke.

OBJECTIVETo investigate the effect of stable knockdown of DNA methyltransferase 3b (DNMT3b) on the proliferation and apoptosis of bladder cancer cells.

METHODSLentivirus expressing DNMT3b siRNA or the negative control siRNA was infected in human bladder cancer BIU-87 cells. MTT assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. The inhibitory effect of DNMT3b knockdown on xenograft tumors in nude mice was observed. Real-time PCR and Western blotting were carried out to investigate the expression level of cell apoptosis related genes. Methylation specific PCR was used to examine the methylation in the promoter region of the cell apoptosis related genes.

RESULTSThe results of real-time PCR and Western blotting showed that DNMT3b mRNA and protein level were stably knocked down in BIU-87 cells. Stable DNMT3b knockdown suppressed BIU-87 cell growth and the tumor formation ability of the cells in nude mice. DNMT3b knockdown promoted the apoptosis of BIU-87 cells, increased the mRNA and protein expression of the cell growth and apoptosis related genes including DAPK, Bax and RASSF1A, and significantly decreased the methylation of these genes.

CONCLUSIONStable DNMT3b knockdown can affect the methylation of the cell growth and apoptosis related genes to regulate their expression, which might be a possible mechanism for suppressed cell growth and enhanced apoptosis of BIU-87 cells.

Animals ; Apoptosis ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; DNA (Cytosine-5-)-Methyltransferases ; genetics ; Gene Knockdown Techniques ; Humans ; Mice ; Mice, Nude ; Neoplasm Transplantation ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Urinary Bladder Neoplasms ; genetics ; pathology

Objective To understand the correlation between self-reported gingival bleeding and type 2 diabetes mellitus (T2DM) in adults in China.Methods The database of China's 2010 Chronic Disease and Risk Factor Surveillance (CCDRFS) survey among people aged ≥ 18 years was used to analyze the demographic characteristics of subjects with self-reporting gingival bleeding and the prevalence of major chronic diseases among adults.Correlation and interaction analyses were conducted on the relationships between frequent gingival bleeding and T2DM,hypertension and dyslipidemia,and interaction of age and gingival bleeding,age and hypertension,age and dyslipidemia,age and gender on the prevalence of T2DM.Results Among 93 647 adults surveyed,87.4％ were in Han ethnic group.The incidence of frequent gingival bleeding was higher in females (63.6％) than in males (36.4％).The incidence of frequent gingival bleeding was highest (30.1％) in adults with middle school education level.Among the adults aged 45-60 years,12.8％(2 839/22 179) had T2MD but no gingival bleeding,15.6％ (163/1 044) had both frequent gingival bleeding and T2DM,frequent gingival bleeding was correlated with T2DM (OR=1.29,95％CI:1.08-1.54) and the interaction with age had influence on T2DM (P＜0.005).In males,frequent gingival bleeding was correlated with T2DM (OR=l.30,95％ CI:1.08-1.56,P=0.005).In hypertension group,frequent gingival bleeding was correlated with T2DM (OR=1.25,95％ CI:1.07-1.46),and interaction of hypertension and gingival bleeding had influence on T2DM (P＜0.05).Conclusions The positive correlation between frequent gingival bleeding and T2DM was observed in adults surveyed,and the interaction of age and hypertension had influence on prevalence of T2DM.Frequent gingival bleeding was correlated with T2DM in males either.

Objective To observe the hematological toxicity of 89SrCl2 in patients with multiple bone metastases of malignant tumors,and analyze the related-risk factors.Methods A total of 89 patients (63 males,26 females;age:(62.3±5.2) years) with multiple bone metastases and treated with 89SrCl2 were enrolled.Hematological data at 2 and 4 weeks after treatment with 89SrCl2 were analyzed.Common Terminology Criteria for Adverse Events (CTCAE) v4.03 was used to evaluate the hematological toxicity,and the influencing risk factors were analyzed.Logistic regression analysis was used to analyze the data.Results The incidences of grade Ⅰ-Ⅱ anemia,leukopenia and thrombocytopania at 2 and 4 weeks after treatment were 15.7％(14/89),18.0％(16/89),11.2％(10/89) and 18.0％(16/89),24.7％(22/89),18.0％(16/89),respectively.The incidences of grade Ⅲ-Ⅳ anemia,leukopenia and thrombocytopenia were 2.2％(2/89),0,0 and 2.2％(2/89),2.2％(2/89),3.4％％(3/89),respectively.Logistics multivariate analysis showed that the number of bone metastases and the Hb level before treatment were independent effect factors for hematological toxicity of 89SrCl2,with odds ratio (OR) values of 2.200(95％ CI:1.269-3.841) and 0.961 (95％ CI:0.932-0.991),respectively.Conclusions Serious hematological toxicity after 89SrCl2 treatment is rare.The number of bone metastases and the Hb level before treatment are independent effect factors for hematological toxicity.

Objective To analyze the problems of review of anti-tumor drug prescriptions and medical orders assisted by an information system to improve the review rules,and to provide a reference for improving review quality of anti-tumor drug prescription.Methods The problem with the pre-review of anti-tumor drug prescriptions and medical orders assisted by the information system in Sichuan Cancer Hospital during 2020-2022 were collected.The data came from the MEDICOM PASS system in Sichuan Cancer hospital.Clinical pharmacists made comments on relevant problems and analyzed the results.Results A total of 9 325 antitumor drug pre-approval problems,including 6 279 outpatient prescriptions(67.3%)and 3 046 inpatient orders(32.7%),among which 6 153(66.0%)were unsuitable indications,1 933(20.7%)were drug contraindications,449(4.8%)were problematic routes of administration,345(3.7%)were unsuitable drug compatibility,177(1.9%)were inappropriate drug frequency,133(1.4%)were problematic drug populations,74(0.8%)were unsuitable single doses,39(0.4%)were unacceptable drug interactions,22(0.2%)were unsuitable drug total.The results of clinical pharmacists'comments were 4 459 reasonable cases,with a false positive rate of 47.8%.The false positive problems included 2 264(50.8%)cases of unsuitable indications,1 933(43.3%)cases of drug contraindications,231(5.2%)cases of problematic routes of administration,and 31(0.7%)cases of unsuitable populations.Conclusion The review of anti-tumor drug prescriptions assisted by an information system can effectively intercept irrational drug use and improve the review quality of prescriptions and medical orders.However,the evidence-based medicine date of antitumor drugs is updated quickly.Pharmacists should constantly improve the prescription review rules based on the latest evidence-based medicine data.

Objective To observe the effects of repeated intravitreal injections of ranibizumab and aflibercept on cor-neal morphology of patients with neovascular age-related macular degeneration(nAMD),diabetic macular edema(DME)or retinal vein obstruction(RVO).Methods In this prospective study,64 patients(64 eyes)who underwent therapy in the injection center of the Ophthalmology Department of our hospital from June 2021 to June 2022 were enrolled,including 19 nAMD patients,20 DME patients and 25 RVO patients.Among these patients,29 were treated with aflibercept(40 g·L-1)and 35 were treated with ranibizumab(10 g·L-1).Monocular injections were adopted for all patients,and 3+pro re nata(PRN)therapy was used.Confocal microscope was used for corneal nerve examination,and corneal endo-thelial microscope was used to measure corneal thickness(CT)and corneal endothelial cells.The CT,corneal endothelial cell density(ECD),coefficient of variation(CV),average cell size(ACS),proportion of hexagonal cells(Hex％),cor-neal nerve fiber length(CNFL),corneal nerve fiber density(CNFD)of patients with nAMD,DME and RVO after repeated intravitreal injections of anti-vascular endothelial growth factor(VEGF)drugs were compared,and those parameters at 1 month after injection of different anti-VEGF drugs were compared with the baseline.Results Before injection,ECD in the DME group was lower than that in the nAMD and RVO groups,and the ACS in the DME group was higher than that in the nAMD and RVO groups(all P＜0.05).There was no significant difference in the other indexes among the three groups(all P＞0.05).After 3 injections of anti-VEGF drugs,the ECD in the DME group was lower than that in the nAMD and RVO groups,the ACS in the DME group was higher than that in the nAMD and RVO groups,and the CNFL in the DME group was lower than that in the nAMD and RVO groups(all P＜0.05).The ECD decreased compared with that before injection from the 2nd injection of aflibercept in the nAMD group(all P＜0.05).Hex％decreased significantly after each injection compared with the baseline(all P＜0.05).Other indexes have no significant differences from the baseline(all P＞0.05).In the RVO group,ECD decreased from the 2nd ranibizumab injection compared with the baseline(all P＜0.05).Conclu-sion Repeated intravitreal injections of anti-VEGF drugs can reduce the Hex％and ECD to a certain extent.After injec-tions,CNFL in the DME group is significantly lower than that in the nAMD and RVO groups.

Hydroxytyrosol is an important fine chemical and is widely used in food and medicine as a natural antioxidant. Production of hydroxytyrosol through synthetic biology is of important significance. Here we cloned and functionally characterized a hydroxylase encoding gene HpaBC from Escherichia coli BL21, and both subunits of this enzyme can be successfully expressed to convert the tyrosol into hydroxytyrosol. A HpaBC gene integration expression cassette under the tac promoter was constructed, and integrated into the genome of a tyrosol hyper-producing E. coli YMG5A*R using CRISPR-Cas9 technology. Meanwhile, the pathway for production of acetic acid was deleted, resulting in a recombinant strain YMGRD1H1. Shake flask fermentation showed that strain YMGRD1H1 can directly use glucose to produce hydroxytyrosol, reaching a titer of 1.81 g/L, and nearly no by-products were detected. A titer of 2.95 g/L was achieved in a fed-batch fermentation conducted in a 5 L fermenter, which is the highest titer for the de novo synthesis of hydroxytyrosol from glucose reported to date. Production of hydroxytyrosol by engineered E. coli lays a foundation for further construction of hydroxytyrosol cell factories with industrial application potential, adding another example for microbial manufacturing of aromatic compounds.
Escherichia coli/genetics* ; Fermentation ; Glucose ; Metabolic Engineering ; Phenylethyl Alcohol/analogs & derivatives*